RBC Disorders

Question 1

What is G6PD deficiency?

Answer 1

• -glucose 6-phoshate dehydrogenase deficiency.
• -x-linked recessive
• -reduced half life of G6PD, renders RBCs susceptible to oxidative stress

Question 2

Why does G6PD deficiency cause RBCs to be more susceptible to oxidative stress?

Answer 2

• -RBCs are normally exposed to oxidative stress, in particular hydrogen peroxide.
• -Glutathione neutralizes hydrogen peroxide, but becomes oxidized in the process
• -NADPH, a by product of G6PD, is needed to regenerate reduced glutathione.

Therefore, a decrease G6PD –> decrease NADPH –> decrease reduced glutathione –> oxidative stress/injury of RBCs –> intravascular hemolysis

Question 3

Who gets G6PD?

Answer 3

There is an African variant and a Mediterranean variant

African: mildly-reduced half life–> mild intravascular hemolysis with oxidative stress

Mediterranean: greatly reduced half-life –> marked intravascular hemolysis with oxidative stress

Question 4

What do we see on labs with G6PD?

Answer 4

Heinz bodies and bite cells on blood smear

Heinz bodies: oxidative stress causes precipitation of Hb
Bite cells: MOs in spleen remove Heinz bodies

Question 5

What are causes of oxidative stress in G6PD?

Answer 5

(1) sulfa drugs
(2) antimalarials (e.g., primaquine)
(3) dapsone
(4) fava beans
(5) infections

Question 6

How does G6PD present?

Answer 6

Back pain, hemoglobinuria days after exposure to oxidative stress. (and hemolytic anemia)

Question 7

How is G6PD diagnosed?

Answer 7

Heinz preparation used to screen; enzyme studies used to confirm diagnosis

Question 8

What is anemia?

Answer 8

a reduction in circulating RBC mass

Question 9

How does anemia present?

Answer 9

with the signs and symptoms of hypoxia

Question 10

What are the signs and symptoms of hypoxia?

Answer 10

(1) weakness, fatigue
(2) shortness of breath
(3) pale conjunctiva and skin
(4) headache and lightheadedness
(5) Angina, espcially with preexisting CAD

Question 11

What measures are used as surrogates for RBC mass?

Answer 11

hemogloblin (Hb)

hematocrit (Hct)

Question 12

How are anemias broadly classified?

Answer 12

By the MCV (mean corpuscular volume)

Question 13

What is the root cause of microcytic anemias?

Answer 13

Microcytic anemias are due to decreased production of hemoglobin.

During RBD development, the cells from erythroid progenitor to the final, mature RBC get smaller with each division. These anemias can be thought of as having arisen due to an “extra” division in order to maintain Hb concentration in the face of decreased Hb production?

Question 14

What are the components of hemoglobin?

Answer 14

Hb consists of heme and globin.
Heme is composed of an iron atom, and a protoporphyrin ring.

A decrease in any one of these components will lead to a microcytic anemia

Question 15

List the main types of microcytic anemia

Answer 15

(1) iron deficiency anemia
(2) anemia of chronic disease
(3) sideroblastic anemia
(4) thalassemias
(5) lead poisoning

Question 16

Describe the process of iron absorption to storage.

Answer 16

1. Iron is absorbed in the duodenum, via the DMT (divalent metal transporter)
2. Enterocytes transport iron from cell across basolateral MB to blood via ferroportin
3. iron is transported in the blood and delivered to storage sites via transferrin
4. iron is stored in bone marrow macrophages and hepatocytes bound to ferritin.

Question 17

What are the laboratory measures of iron status?

Answer 17

1. serum iron –measures iron in the blood
2. total iron-binding capacity (TIBC) –measure of transferrin molecules in the blood
3. % saturation – % of transferrin molecules that are bound by iron (normal is 33%)
4. serum ferritin – reflects iron stores in macrophages and liver

Question 18

What are the lab findings of iron deficiency anemia?

Answer 18

1. decreased serum ferritin
2. increased TIBC
3. decreased serum iron
4. decreased % saturation of transferrin
5. microcytic, hypochromic RBCs
6. increased RCDW (red cell distribution width)
7. increased free erythrocyte protoporphyrin (FEP)

Question 19

What are the clinical features of iron deficiency anemia?

Answer 19

1. anemia
2. koilonychia (spoon-shaped nails)
3. pica (disorder where patients chew on things abnormally, such as ice or dirt)

Question 20

What is the red cell distribution width?

Answer 20

This measure asks the question: what is the spectrum of the size of RBCs?

If all the RBCs are relatively the same size, the RDW will be low; if there is a wide spectrum of RBC size, the RDW will be high (increased)

Question 21

Why do we see an increase in the RDW in iron deficiency anemia?

Answer 21

Initially in iron-deficiency anemia, the body tries to make less RBCs that are still normal – a normocytic anemia. As the deficiency progresses, the body will produce smaller cells. We will therefore see a larger spectrum of cell size.

Question 22

What is free erythrocyte protoporphyrin and why is it increased in iron deficiency anemia.

Answer 22

Protoporphryin is the organic ring structure that combines with iron to produce heme. When we have an iron deficiency, we are still producing protoporphyrin. However, not all of this will now be bound to iron–it will be “free”. Therefore, in iron deficiency anemia, we will have in increase in the free, unbound protoporphyrin.